Urgency urinary incontinence (UUI) is prevalent in older adults, and often ascribed to dysfunction solely in the lower urinary tract (LUT). In fact, the brain has an important role, including viscerosensory feedback, LUT control and response to LUT dysfunction, all of which may decline in the aging process. It is therefore important to understand the brain’s role, not only in maintaining continence, but in relation to LUT dysfunction, to understand ways in which the brain control mechanism can be leveraged therapeutically.

We conducted a study to investigate this by utilizing an anticholinergic drug as a probe to assess changes in brain activity occurring with symptom improvement and decline. Though currently blinded, we present here the first available measures: baseline aggregate measures of brain activation in over one hundred women with UUI.

We recruited women over 60 with >5 episodes of UUI per week for a randomized crossover trial with brain MRI at three timepoints. Here we report a single baseline functional MRI (fMRI) task using a previously validated bladder infusion-withdrawal task. Participants’ bladders were filled via catheter to ‘strong desire to void’ and 22mL water was infused over 12s (infuse) and 20mL withdrawn (withdraw) over 12s, repeated four times, representing a block design where brain activity during withdraw could be subtracted from activity during infuse. We preprocessed this data using standard processing (unwarping, motion correction, normalization, and smoothing). We modeled task activity using generalized linear models that model the infuse and withdraw periods using boxcars convolved with the hemodynamic response function. We conducted a voxel-wise paired t-test between infuse and withdraw using statistical non-parametric mapping (SnPM) toolbox, which uses permutation testing (10,000 permutations) and a cluster-forming threshold (p = 0.001) with cluster-wise inference to control the family-wise error rate α = 0.05. We extracted three a priori identified regions of interest: dorsal ACC (dACC), supplemental motor area (SMA), insula (Ins) bilaterally and evaluated associations with mean number of voids and leaks per day.

114 participants were available for group analysis, with mean(SD) age 68.4(6.0) years and mean(SD) number of leaks 3.7(2.4) per day and mean(SD) number of voids 8.6(2.4) per day on 3-day bladder diary. We found expected areas of activation when comparing infuse and withdraw conditions in our target areas of interest (figure 1) including greater activation in dACC, SMA, and Insula, but also cerebellum, motor/sensory cortex, thalamus, putamen/caudate, inferior/middle/superior frontal gyrus, medial frontal gyrus, mid cingulate, supramarginal gyrus, inferior parietal lobe, superior temporal gyrus, amygdala, and visual cortex. We found that greater bilateral dACC activity during infuse compared to withdrawal was associated with greater mean number of voids [r=0.24, p<0.05, figure 2A] and leaks [r=0.17, p=0.0651] per day. We found that greater bilateral insula activity during infuse compared to withdrawal was associated with greater mean number of voids [r=0.22, p<0.05, figure 2B] per day.

The activity in figure 1 replicates the activity patterns found in other studies(1) of older women with UUI, showing significant, strong activation in the a priori chosen regions of interest. While there were no significant associations of number of leaks with activity, there were some slight associations with mean number of voids per day in regions associated with sensation (insula) and attentional processing (dACC). The large number of participants will allow much more in depth subgroup analysis without loss of statistical confidence.

These results represent blinded, baseline data for a larger study in which we aim to understand how symptom changes are reflected in brain activity longitudinally. We robustly replicate results with a much larger n, with which we will report on brain mechanisms with the imminent unblinding of the data.

J Urol 2015 Sep;194(3):708-15. doi: 10.1016/j.juro.2015.03.102